Nuclear fission in the experimental, isotope-producing, or energy-supplying nuclear reactors and in nuclear weapon tests is accompanied by the formation of a considerable amount of radioactive by-products. Majorities of these hot materials involve fission products and activated elements, including extremely hazardous radioactive isotopes such as iodine-131, strontium-89-90, cesium-134 and -137, cerium-141 and -144. Emitted into the environment, they may result in a radioactive pollution.
There are three ways these isotopes can enter the human body: the respiratory tract (breathing with air), the digestive tract (ingesting with foods and drinks), the epidermal layer of the skin (contacting with harmed or unharmed skin).
A good deal of methods are already known for reducing or even preventing injuries of health due to such radiation exposure. Some isotopes, essentially Radiostrontium, however, can only be protected against by hindering/preventing its gastrointestinal absorption with per oral administration of suitable adsorbents (blockers/congeners, which will block absorption of *Sr or compete with *Sr and hence, hinder its absorption). If the medical aid begins as late as several hours after the contamination, no efficient methods are available at the present state of the medical art for blocking the absorbed proportion of the radioisotopes, which could get transported by the blood-stream and the lymph-flow to influence their deposition in bones, to prevent their histic binding and to promote their decorporation.
Many of such radiological impacts in the event of any nuclear accident are ascribed to the exposure to the other volatile radionuclides, mainly Radiocesium (*Cs) and Radioiodine (*1), which could be effectively transported through the atmosphere to the “far-field”, besides causing the immediate radiation hazard to the inhabitants in the “near-field” region. *Cs, with its wide distribution, its 30 year half-life and, its beta/gamma dose potential and its ubiquitous distribution throughout all tissues (because of being a Potassium congener) besides getting recycled through plant-animal-human food chain, poses the dominant radio-biological threat.
Radiostrontium (*Sr) is another radionuclide, which also needs to be attended to because of its long half-life of 28.5 years (90Sr) besides its specific localization in bone, where it can damage the affected subjects' bone-marrow, once it enters in our in vivo milieu. Apart from 239Pu, which is basically fixed to the soil and has shown no significant transfer to man after the Chernobyl nuclear accident, only 137Cs and 90Sr have deposited on the ground and entered the biological cycle, besides Radioiodine induced damage to the thyroid gland in the early stages after a nuclear accident.
Of the various radioisotopes of Cesium (Cs), 137Cs is the most important and a common fission by-product material, besides being a frequent active component of sealed sources used for industrial/medical application. It is an important radionuclide, particularly in radiation oncology, found in hospitals performing either gynecological brachytherapy or intestinal therapy for solid tumors. All this has resulted in a steady increase in the use of *Cs for various experimental, diagnostic and therapeutic purposes. The presence of a large number of nuclear reactors world wide has further increased the chances of its accidental release, posing a greater radiation hazard, not only to workers at the reactor site and the people around but also to the population at a distance, if they are exposed to the air-borne *Cs or contaminated food/water. These risks have been clearly exemplified by the Chernobyl nuclear reactor and Goinnia radiological accidents.
Radio-cesium (*Cs), particularly 137Cs, has a high impact on human health for the following reasons:    1. It is easily absorbed by the body through different routes (ingestion, inhalation and/or skin penetration).    2. It has a relatively long biological half-life in humans of about 100-110 days.    3. Its physical half-life is 30 years.    4. It emits beta and penetrating gamma radiation of high energy.    5. It is distributed uniformly more or less throughout the body due to its proximity to elements Potassium and Sodium.
The most common treatment for metal poisoning is “chelation therapy.” Conventional chelation therapy involves intravenous injection of a chelating agent into the patient. Widely known and conventional chelating agents such as EDTA (ethylenediaminetetraacetic acid) and DTPA (diethylenetriamine pentaacetic acid) are often employed. Conventional chelation therapy is very painful to the patient and has only limited effectiveness.
Moreover most of the chelating agents used in this type of therapy are generally hydrophilic, rapidly excreted, and have only limited ability to penetrate cells in order to remove the subject metals. Thus, the use of EDTA in the treatment of lead poisoning, for example, is effective in removing lead in the blood, but is not effective in removing lead that has penetrated (deposited in) the cells (vital tissue/organ).
Furthermore, it is not possible to target specific organs with conventional chelation therapy. Certain metals are more significantly deposited in certain organs than in other organs. Some metals, for example, are significantly deposited in the bone. Thus, in order to provide an effective treatment it is necessary to have a substance that can penetrate the cellular barrier lining the bone surface. This capability is not readily available with conventional chelating agents.
It is also of importance that the compositions promote decorporation of the metal, not redistribution of the metal. In some studies with known chelating agents it has been suggested that the metal is simply dislodged from one tissue and redeposited in another tissue. The compositions of the present invention, conversely, result in actual removal of the metal from the body of the mammal.
U.S. Pat. Nos. 5,494,935 and 5,403,862 teach several new chelating agents like partially lipophilic polyaminocaboxylic acids (PACA) for decorporation of heavy metal ions from the in vivo system of affected subjects. In contrast to their non-lipophilic counterparts EDTA and DTPA, these chelating agents exhibit appreciable absorption from the intestine and therefore, can be administered orally. But, the deficiency associated with such chelating agents is that they can be directed primarily to certain specific organs only. Moreover, these chelating agents target only some particular adsorbed metals, and not specifically their radioactive counterparts.
U.S. Pat. No. 5,288,718 discloses monocyclic cryptate ligands and their derivatives that are suitable for the removal of Radiostrontium, occasionally other radioactive metal isotopes, from the living organisms. An active agent based on 1,4,10,13-tetraoxa-7, 16diazacyclooctadecane-N, N′-dimalonic acid tetrasodium salt was shown to be capable of promoting the excretion of Radiostrontium and Radiocesium which had been administered into various sites (peritoneal cavity, subcutaneous interstitial tissue, lung) of the animal body.
U.S. Pat. No. 4,780,238 relates to the preparation of new, naturally produced chelating agents as well as to the method and resulting chelates of desorbing cultures in a bioavailable form involving Pseudomonas species or other microorganisms. A preferred microorganism is Pseudomonas aeruginosa which forms multiple chelates with thorium in the range of molecular weight 100-1,000 and also forms chelates with uranium of molecular weight in the area of 100-1,000 and 1,000-2,000.
Hitherto, Prussian blue (as Radiogardase-Cs, marketed by Heyl, Chem. -Pham, Fabrik, Berlin) has been in use for the clearance of *Cs from in vivo milieu. Chemically, it is insoluble ferric hexa-cyanoferrate (II) with an empirical formula of Fe4[Fe(CN)6]3 and a molecular weight of 859.3 Dalton. It is provided as blue powder in 0.5 g gelatin capsules.
Hitherto reported mixture of three compounds: Prussian blue, Calcium Alginate (CaA) and Potassium Iodide (KI), is suggested to be mixed in the diet and fed for three days earlier to the animals before their exposure to the radionuclides, for their clearance from the in vivo milieu.
There are several drawbacks associated to the hitherto known processes, which the present invention seeks to remove, namely:    1) Prussian blue, Calcium alginate and KI need to be mixed with the diet and fed prior to the exposure to the radionuclides, which is not always feasible.    2) Prussian blue is slow in removing *Cs from in vivo system of the experimental animals. One of the constituents—Calcium Potassium Ferrocyanide [CaK2Fe(CN)6], of the present mixture is considerably faster than Prussian blue in decorporating *Cs from the in vivo system of the experimental animals.    3) Prussian blue induces gastro-intestinal and cardio-toxicity in the experimental animals. The present mixture does not produce any such histo-pathologic changes in these organs. Prussian Blue also produces significantly more liver and kidney damage compared to Calcium Potassium Ferrocyanide, when fed in the diet or administered orally at the same dose level as Prussian Blue, for approximately six months.    4) Prussian Blue has been observed to induce constipation in some subjects probably because of gastro-intestinal toxicity.    5) Mild reduction in hemoglobin levels has been noted in the animals after treating with the hitherto reported mixture of antidotes.    6) Prussian blue, at the same dose level, is only 25-50% as effective as Calcium Potassium Ferrocyanide [CaK2Fe(CN)6], a constituent of the present mixture, in complexing/extraction of stable/radio Cesium, in acidic medium (pH 2-3) normally present in the gastric region.    7) Calcium alginate, an ingredient of the hitherto known mixture, is quite viscous and unpalatable compound compared to one of the common calcium salts used in the mixture. The calcium based salt used in the present mixture, is as potent as Calcium alginate in curtailing whole body retention of *Sr.    8) KI, used in the hitherto known mixture, is known to be quite hygroscopic chemical and thus reduces the shelf life of the mixture. This poses storage problems.    9) Remedial measures are specific for a particular radionuclide and not others and in case individuals have been exposed to more than one radionuclide, they need to be treated for each radio-isotope separately.
Thus, there is a long felt need for a suitable radio decorporating agent, which could remove these drawbacks connected to the prior art. The following specific requirements are established to such a prophylactic agent:                (a) the complex formation must take place in the biological system even in the presence of concurrent ions (such as Ca2+, Na+, K+, etc.) and ligands that are present in a great amount.        (b) it should have a pharmaceutically acceptable level of toxicity (wide-range efficiency);        (c) it must be easily administrable.        
The inventors have found that the retention of three most important fission radionuclides: *Cs, *Sr and *I may be simultaneously curtailed and decorporated from subjects accidentally exposed to such radionuclides, by the oral administration of a mixture of:    (a) Calcium Potassium Ferrocyanide [CaK2Fe(CN)6]—a novel compound;    (b) Calcium Iodate, and    (c) Calcium Carbonate.
The detailed formulation of such a mixture is provided in the following section.